Table 2.
Comparison of methodologies and results from studies examining relationships between NLRP3, NLRP6, NLRP12, and the gut microbiota
Nlrp3 genotypeDisease modelNLRP3 functionMicrobiome implicatedGerm-free (GF) strategyMicrobiome changesCellular mechanismLittermates?Reference
Nlrp3−/− DSS, TNBS Protective Antibiotic treatment N/A Commensal overgrowth and bacteremia ↓Non-hematopoietic cell IL-18 production No Zaki et al., 2010  
Nlrp3−/− DSS, TNBS Protective TRFLP seq N/A ↑Enterobacteriaceae ↑Mycobacterium; ↑Clostridium; etc. ↓Colonic IL-1β, IL-10, TGFβ, and antimicrobial secretions; ↓Neutrophil and macrophage responses Yes Hirota et al., 2011  
Nlrp3−/− DSS, TNBS Pathogenic Antibiotic treatment, cohousing N/A N/A ↑Lamina propria CD103+ tolerogenic DCs No Bauer et al., 2012  
Nlrp3R258W (hyper-active) DSS, AOM-DSS Protective Antibiotic treatment, cohousing, fecal transplantation, 16S seq Fecal transplantation to GF-WT recipients ↓Actinobacteria; ↓Verrucomicrobia; ↓Akkermansia; ↑Lactobacillus ↑IL-1β and AMP from lamina propria immune cells; ↑Regulatory T cells Yes Yao et al., 2017  
Nlrp6 genotype Disease model NLRP6 function Microbiome implicated Germ-free (GF) strategy Microbiome changes Cellular mechanism Littermates? Reference 
Nlrp6−/− Steady state, DSS Protective Antibiotic treatment, cohousing, 16S seq N/A ↑Prevotellaceae ↓Non-hematopoietic IL-18 production; ↑CCL5 production; ↑Immune cell recruitment No Elinav et al., 2011  
Nlrp6−/− Listeria, Salmonella, etc., infection Pathogenic Cohousing, 16S seq N/A ↑Bacteroidetes (Prevotellaceae family) ↑Monocyte and neutrophil recruitment; ↑NF-κB and ERK activation No Anand et al., 2012  
Nlrp6−/− AOM-DSS Protective Antibiotic treatment, cohousing N/A N/A ↑Tumorigenesis mediated by IL-18, CCL5, and IL-6 No Hu et al., 2013  
Nlrp6−/− Citrobacter rodentium infection Protective Cohousing N/A N/A ↓Autophage in goblet cells; ↓Mucus secretion No Wlodarska et al., 2014  
Nlrp6−/− Steady state, IL-18, LPS, DSS Protective Antibiotic treatment, cohousing, 16S seq GF-WT and GF-Nlrp6−/−, cohousing in GF-WT Different microbial compositions compared with WT ↓IL-18 production; ↓AMPs No Levy et al., 2015  
Nlrp6−/−, Nlrp6−/−, Il10−/− DKO Il10−/− spontaneous colitis Protective Cohousing, 16S seq Fecal transplantation to GF-WT and GF-Nlrp6−/−recipients ↓Bacterial richness and diversity; ↑Akkermansia; Bacteroides; Prevotella; etc. ↓IL-18 production; ↑Significant colitis Yes Seregin et al., 2017  
Nlrp6−/− Steady state, DSS No impact on colitis Cohousing, 16S seq N/A No impact on microbiota composition N/A Yes Lemire et al., 2017  
Nlrp6−/− Steady state, DSS No impact on colitis Cohousing, 16S seq GF-Pycard−/− mice No impact on microbiota composition N/A Yes Mamantopoulos et al., 2017  
Nlrp6−/− Steady state N/A Fecal transplantation, 16S seq N/A ↑Prevotellaceae; ↑Helicobacteraceae; etc. N/A No Gálvez et al., 2017  
Nlrp6−/− Apigenin treatment, DSS Protective Cohousing, 16S seq N/A ↓Bacterial diversity, compared with WT Antiproliferative effect of apigenin dependents on NLRP6 pathway No Radulovic et al., 2018  
Nlrp6−/− Graft-versus-host disease (GVHD) Pathogenic Antibiotic treatment, cohousing, fecal transplantation Fecal transplantation to GF-WT and GF-Nlrp6−/− recipients ↑Porphyromonadaceae; ↑Prevotellaceae GVHD is independent of microbiome; ↑Gastrointestinal homeostasis after allo-BMT Yes Toubai et al., 2019  
Nlrp12−/− DSS Protective Cohousing, fecal transplantation, 16S seq Fecal transplantation to GF-WT and GF-Nlrp12−/− recipients ↑Lachnospiraceae family; ↑Erysipelotrichaceae family; ↓Bacteroidales order; ↓Clostridiales order ↑Inflammatory signaling; ↑inflammatory cytokine production from colonic DCs Yes Chen et al., 2017a  
Nlrp3 genotypeDisease modelNLRP3 functionMicrobiome implicatedGerm-free (GF) strategyMicrobiome changesCellular mechanismLittermates?Reference
Nlrp3−/− DSS, TNBS Protective Antibiotic treatment N/A Commensal overgrowth and bacteremia ↓Non-hematopoietic cell IL-18 production No Zaki et al., 2010  
Nlrp3−/− DSS, TNBS Protective TRFLP seq N/A ↑Enterobacteriaceae ↑Mycobacterium; ↑Clostridium; etc. ↓Colonic IL-1β, IL-10, TGFβ, and antimicrobial secretions; ↓Neutrophil and macrophage responses Yes Hirota et al., 2011  
Nlrp3−/− DSS, TNBS Pathogenic Antibiotic treatment, cohousing N/A N/A ↑Lamina propria CD103+ tolerogenic DCs No Bauer et al., 2012  
Nlrp3R258W (hyper-active) DSS, AOM-DSS Protective Antibiotic treatment, cohousing, fecal transplantation, 16S seq Fecal transplantation to GF-WT recipients ↓Actinobacteria; ↓Verrucomicrobia; ↓Akkermansia; ↑Lactobacillus ↑IL-1β and AMP from lamina propria immune cells; ↑Regulatory T cells Yes Yao et al., 2017  
Nlrp6 genotype Disease model NLRP6 function Microbiome implicated Germ-free (GF) strategy Microbiome changes Cellular mechanism Littermates? Reference 
Nlrp6−/− Steady state, DSS Protective Antibiotic treatment, cohousing, 16S seq N/A ↑Prevotellaceae ↓Non-hematopoietic IL-18 production; ↑CCL5 production; ↑Immune cell recruitment No Elinav et al., 2011  
Nlrp6−/− Listeria, Salmonella, etc., infection Pathogenic Cohousing, 16S seq N/A ↑Bacteroidetes (Prevotellaceae family) ↑Monocyte and neutrophil recruitment; ↑NF-κB and ERK activation No Anand et al., 2012  
Nlrp6−/− AOM-DSS Protective Antibiotic treatment, cohousing N/A N/A ↑Tumorigenesis mediated by IL-18, CCL5, and IL-6 No Hu et al., 2013  
Nlrp6−/− Citrobacter rodentium infection Protective Cohousing N/A N/A ↓Autophage in goblet cells; ↓Mucus secretion No Wlodarska et al., 2014  
Nlrp6−/− Steady state, IL-18, LPS, DSS Protective Antibiotic treatment, cohousing, 16S seq GF-WT and GF-Nlrp6−/−, cohousing in GF-WT Different microbial compositions compared with WT ↓IL-18 production; ↓AMPs No Levy et al., 2015  
Nlrp6−/−, Nlrp6−/−, Il10−/− DKO Il10−/− spontaneous colitis Protective Cohousing, 16S seq Fecal transplantation to GF-WT and GF-Nlrp6−/−recipients ↓Bacterial richness and diversity; ↑Akkermansia; Bacteroides; Prevotella; etc. ↓IL-18 production; ↑Significant colitis Yes Seregin et al., 2017  
Nlrp6−/− Steady state, DSS No impact on colitis Cohousing, 16S seq N/A No impact on microbiota composition N/A Yes Lemire et al., 2017  
Nlrp6−/− Steady state, DSS No impact on colitis Cohousing, 16S seq GF-Pycard−/− mice No impact on microbiota composition N/A Yes Mamantopoulos et al., 2017  
Nlrp6−/− Steady state N/A Fecal transplantation, 16S seq N/A ↑Prevotellaceae; ↑Helicobacteraceae; etc. N/A No Gálvez et al., 2017  
Nlrp6−/− Apigenin treatment, DSS Protective Cohousing, 16S seq N/A ↓Bacterial diversity, compared with WT Antiproliferative effect of apigenin dependents on NLRP6 pathway No Radulovic et al., 2018  
Nlrp6−/− Graft-versus-host disease (GVHD) Pathogenic Antibiotic treatment, cohousing, fecal transplantation Fecal transplantation to GF-WT and GF-Nlrp6−/− recipients ↑Porphyromonadaceae; ↑Prevotellaceae GVHD is independent of microbiome; ↑Gastrointestinal homeostasis after allo-BMT Yes Toubai et al., 2019  
Nlrp12−/− DSS Protective Cohousing, fecal transplantation, 16S seq Fecal transplantation to GF-WT and GF-Nlrp12−/− recipients ↑Lachnospiraceae family; ↑Erysipelotrichaceae family; ↓Bacteroidales order; ↓Clostridiales order ↑Inflammatory signaling; ↑inflammatory cytokine production from colonic DCs Yes Chen et al., 2017a  

Summary of recent studies regarding the correlations between NLRP3, NLRP6, and NLRP12 and the gut microbiome in murine models of intestinal infection and inflammation. AMP, antimicrobial peptide; BMT, bone marrow transplant; DKO, double-knockout; LPS, lipopolysaccharide; N/A, not applicable; seq, sequencing; TRFLP, terminal–restriction fragment length polymorphism.

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